Effects of antimitotic and antimitochondrial agents on the cellular distribution of microtubules and mitochondria.
Using antibodies to a mitochondrial molecular chaperone class of protein, which is specifically altered in mutants resistant to microtubule (MT) inhibitors, the effect of a number of MT and mitochondrial inhibitors on the cellular distribution of mitochondria and various cytoskeletal filaments was examined. Treatment of Chinese hamster ovary (CHO) or chicken embryo fibroblast (CEF) cells with the MT inhibitors podophyllotoxin, colchicine, nocodazole and vinblastine caused depolymerization of cellular MTs, but had no significant effect on the distribution patterns of mitochondria. This is attributed to the association of mitochondria with intermediate filaments (IFs) which are not destroyed under these conditions. In contrast to MT inhibitors, treatment of CEFs with the potassium ionophores nonactin and valinomycin caused aggregation of mitochondria towards the perinuclear region of the cells, without having any apparent effect on cellular MTs. This observation suggests that mitochondrial membrane potential, which is abolished by these drugs, play a role in the cellular distribution of mitochondria. In cells recovering from the effects of MT inhibitors, mitochondria have been found to surround the MT organizing complexes and upon complete recovery a realignment of MTs with mitochondria takes place. These observations suggest that MT growth in cells does not occur in a completely random manner but that mitochondria may play some role in their directional growth.
Dudani
A K
AK
Department of Biochemistry, McMaster University, Hamilton, Canada.
Austin
R C
RC
Venner
T J
TJ
Gupta
R S
RS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D011034:Podophyllotoxin / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D014747:Vinblastine; D011034:Podophyllotoxin; D015739:Nocodazole; D003078:Colchicine